Journal of Parkinson's Disease - Volume 11, issue 4

Authors: Heilbron, Karl | Jensen, Melanie P. | Bandres-Ciga, Sara | Fontanillas, Pierre | Blauwendraat, Cornelis | Nalls, Mike A. | Singleton, Andrew B. | Smith, George Davey | Cannon, Paul | Noyce, Alastair J. | The 23andMe Research Team

Article Type: Research Article

Abstract: Background: Tobacco smoking and alcohol intake have been identified in observational studies as potentially protective factors against developing Parkinson’s disease (PD); the impact of body mass index (BMI) on PD risk is debated. Whether such epidemiological associations are causal remains unclear. Mendelian randomsation (MR) uses genetic variants to explore the effects of exposures on outcomes; potentially reducing bias from residual confounding and reverse causation. Objective: Using MR, we examined relationships between PD risk and three unhealthy behaviours: tobacco smoking, alcohol intake, and higher BMI. Methods: 19,924 PD cases and 2,413,087 controls were included in the analysis. …We performed genome-wide association studies to identify single nucleotide polymorphisms associated with tobacco smoking, alcohol intake, and BMI. MR analysis of the relationship between each exposure and PD was undertaken using a split-sample design. Results: Ever-smoking reduced the risk of PD (OR 0.955; 95%confidence interval [CI] 0.921–0.991; p  = 0.013). Higher daily alcohol intake increased the risk of PD (OR 1.125, 95%CI 1.025–1.235; p  = 0.013) and a 1 kg/m2 higher BMI reduced the risk of PD (OR 0.988, 95%CI 0.979–0.997; p  = 0.008). Sensitivity analyses did not suggest bias from horizontal pleiotropy or invalid instruments. Conclusion: Using split-sample MR in over 2.4 million participants, we observed a protective effect of smoking on risk of PD. In contrast to observational data, alcohol consumption appeared to increase the risk of PD. Higher BMI had a protective effect on PD, but the effect was small. Show more

Keywords: Parkinson’s disease, 23andMe, smoking, alcohol, BMI

DOI: 10.3233/JPD-202487

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1981-1993, 2021

Authors: Snyder, Allison | Gruber-Baldini, Ann L. | Rainer von Coelln, F. | Savitt, Joseph M. | Reich, Stephen G. | Armstrong, Melissa J. | Shulman, Lisa M.

Article Type: Research Article

Abstract: Background: Cognitive impairment (CI) is common in Parkinson’s disease (PD) and an important cause of disability. Screening facilitates early detection of CI and has implications for management. Preclinical disability is when patients have functional limitations but maintain independence through compensatory measures. Objective: The objective of this study was to investigate the relationship between scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) with levels of PD severity and disability. Methods: PD patients (n  = 2,234) in a large observational study were stratified by disease severity, based on Total Unified Parkinson’s Disease Rating Scale (Total …UPDRS) and Hoehn and Yahr (HY) stage. Using MMSE (n  = 1,184) or MoCA (n  = 1,050) and basic (ADL) and instrumental activities of daily living (IADL) scales for disability, linear regression analysis examined associations between cognitive status and disability. Results: Cognition and disability were highly correlated, with the strongest correlation between IADL and MoCA. Only 16.0% of mean MMSE scores were below threshold for CI (28) and only in advanced PD (Total UPDRS 60+, HY≥3). MoCA scores fell below CI threshold (26) in 66.2% of the sample and earlier in disease (Total UPDRS 30+, HY≥2), corresponding with impairments in ADLs. Conclusion: In a large clinical dataset, a small fraction of MMSE scores fell below cutoff for CI, reinforcing that MMSE is an insensitive screening tool in PD. MoCA scores indicated CI earlier in disease and coincided with disability. This study shows that MoCA, but not MMSE is sensitive to the emergence of early cognitive impairment in PD and correlates with the concomitant onset of disability. Show more

Keywords: Parkinson’s disease, cognitive impairment, cognitive screening, disability

DOI: 10.3233/JPD-212705

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 1995-2003, 2021

Authors: Hamada, Tomoya | Higashiyama, Yuichi | Saito, Asami | Morihara, Keisuke | Landin-Romero, Ramon | Okamoto, Mitsuo | Kimura, Katsuo | Miyaji, Yousuke | Joki, Hideto | Kishida, Hitaru | Doi, Hiroshi | Ueda, Naohisa | Takeuchi, Hideyuki | Tanaka, Fumiaki

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) in Parkinson’s disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown. Objective: This study aimed to investigate the relative diagnostic accuracy of qualitative (clustering and switching) verbal fluency strategies and their correlates with functional imaging in PD-MCI. Methods: Forty-five patients with PD (26 with MCI and 19 without MCI) and 25 …healthy controls underwent comprehensive neurocognitive testing and resting-state functional magnetic resonance imaging. MCI in patients with PD was diagnosed according to established clinical criteria. The diagnostic accuracy of verbal fluency measures was determined via receiver operating characteristic analysis. Changes in brain functional connectivity between groups and across clinical measures were assessed using seed-to-voxel analyses. Results: Patients with PD-MCI generated fewer words and switched less frequently in semantic and phonemic fluency tasks compared to other groups. Switching in semantic fluency showed high diagnostic accuracy for PD-MCI and was associated with reduced functional connectivity in the salience network. Conclusion: Our results indicate that reduced switching in semantic fluency tasks is a sensitive and specific marker for PD-MCI. Qualitative verbal fluency deficits and salience network dysfunction represent early clinical changes observed in PD-MCI. Show more

Keywords: Brain connectivity, mild cognitive impairment, Parkinson’s disease, salience network, verbal fluency

DOI: 10.3233/JPD-202473

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2005-2016, 2021

Authors: Loftus, Andrea M. | Nielsen, Chloe | Corti, Emily J. | Starkstein, Sergio | Gasson, Natalie | Egan, Sarah J.

Article Type: Research Article

Abstract: Background: Recent research suggests that a significant number of those who receive advanced treatments for Parkinson’s disease (PD) do not report improvements for some symptoms, which may relate to their pre-treatment expectations. It is important that expectations of treatment are measured and discussed prior to advanced treatment. Objective: The primary aim of this study was to develop a measure of treatment expectations of two advanced-stage treatments in PD, deep brain stimulation (DBS), and Levodopa/Carbidopa Intestinal Gel (LCIG). A secondary aim was to explore potential predictors of treatment expectations. Methods: The questionnaire-based measure was developed by researchers …in conjunction with a highly experienced clinician, and evaluated treatment expectations in 189 people aged 46–91 years (M  = 71.35, SD  = 8.73; 61% male) with idiopathic PD. Results: The overall measure demonstrated excellent internal consistency (α = 0.96). Exploratory factor analysis suggested the scale was unidimensional for both DBS and LCIG. Participant expectations of the two treatments differed significantly, with expectations being higher for DBS. Perceived symptom severity was the strongest predictor of treatment expectations. Conclusion: This scale has potential to inform clinicians about client expectations prior to advanced stage therapy for PD, with a view to the management of these expectations. Further evaluation of the scale is required across different treatment contexts. Show more

Keywords: Parkinson’s disease, treatment expectations, deep brain stimulation, Levodopa/carbidopa intestinal gel, quality of life, psychological

DOI: 10.3233/JPD-212777

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2017-2026, 2021

Authors: Silbergleit, Alice K. | Schultz, Lonni | Hamilton, Kendra | LeWitt, Peter A. | Sidiropoulos, Christos

Article Type: Research Article

Abstract: Background: Hypokinetic dysarthria and dysphagia are known features of Parkinson’s disease; however, self-perception of their handicapping effects on emotional, physical, and functional aspects of quality of life over disease duration is less understood. Objective: 1) Based upon patient self-perception, to determine the relationship of the handicapping effects of dysphagia and dysphonia with time since diagnosis in individuals with Parkinson’s disease; 2)To determine if there is a relationship between voice and swallowing handicap throughout the course of Parkinson’s disease. Method: 277 subjects completed the Dysphagia Handicap Index and the Voice Handicap Index. Subjects were divided into three …groups based on disease duration: 0–4 years, 5–9 years, and 10 + years. Results: Subjects in the longer duration group identified significantly greater perceptions of voice and swallowing handicap compared to the shorter duration groups. There was a significant positive correlation between the DHI and VHI. Conclusion: Self-perception of swallowing and voice handicap in Parkinson’s disease are associated with later stages of disease and progress in a linear fashion. Self-perception of voice and swallowing handicap parallel each other throughout disease progression in Parkinson’s disease. Individuals may be able to compensate for changes in voice and swallowing early while sensory perceptual feedback is intact. Results support early targeted questioning of patient self-perception of voice and swallowing handicap as identification of one problem indicates awareness of the other, thus creating an opportunity for early treatment and maintenance of swallowing and communication quality of life for as long as possible. Show more

Keywords: Disease duration, dysarthria, dysphagia, handicapping effects, self-perception

DOI: 10.3233/JPD-212621

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2027-2034, 2021

Authors: Utz, Kathrin S. | Martini, Max | Mrochen, Anne | Lambrecht, Vera | Süß, Patrick | Renner, Bertold | Freiherr, Jessica | Schenk, Thomas | Winkler, Jürgen | Marxreiter, Franz

Article Type: Research Article

Abstract: Background: There is growing interest in non-motor symptoms in Parkinson’s disease (PD), due to the impact on quality of life. Anhedonia, the inability to experience joy and lust, has a prevalence of up to 46% in PD. The perception of pleasantness of an odor is reduced in anhedonia without PD. We previously showed a reduced hedonic olfactory perception in PD, i.e., patients evaluated odors as less pleasant or unpleasant compared to controls. This deficit correlated with anhedonia. Objective: We aimed to confirm these findings. Moreover, we hypothesized that the perception of pleasantness in PD is affected on a …multisensory level and correlates with anhedonia. Therefore, we assessed olfactory, visual and acoustic evaluation of pleasantness in PD and healthy individuals. Methods: Participants had to rate the pleasantness of 22 odors, pictures, and sounds on a nine-point Likert scale. Depression, anhedonia, and apathy were assessed by means of questionnaires. Results of the pleasantness-rating were compared between groups and correlated to scores of the questionnaires. Results: In particular pleasant and unpleasant stimuli across all three modalities are perceived less intense in PD, suggesting that a reduced range of perception of pleasantness is a multisensory phenomenon. However, only a reduction of visual hedonic perception correlated with anhedonia in PD. A correlation of reduced perception of pleasantness with apathy or depression was not present. Conclusion: We provide evidence for a multisensory deficit in the perception of pleasantness. Further studies should delineate the underlying neural circuity and the diagnostic value to detect neuropsychiatric symptoms in PD. Show more

Keywords: Parkinson’s disease, anhedonia, hyposmia, non-motor symptoms, depression, apathy, Sniffin’ Sticks, affective pictures

DOI: 10.3233/JPD-212812

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2035-2045, 2021

Authors: Luque-Casado, Antonio | Novo-Ponte, Sabela | Sánchez-Molina, José Andrés | Sevilla-Sánchez, Marta | Santos-García, Diego | Fernández-del-Olmo, Miguel

Article Type: Research Article

Abstract: Background: Despite the frequent use of the Timed Up and Go (TUG) test in clinical trials, evaluation of longitudinal test-retest reliability is generally lacking and still inconclusive for patients with Parkinson’s disease (PD). Objective: We aimed to further investigate long-term reliability and sensitivity of the TUG test among this population. Furthermore, we explored alternative assessment strategies of the test aimed at elucidating whether the inclusion or combination of timed trials may have potential implications on outcome measure. Methods: Relative and absolute reliability of the TUG performance were obtained in forty-three subjects with PD over three timed …trials in two different testing sessions separated by a two-months period. Results: Our results reported excellent intra-session and moderate inter-session reliability coefficients. The use of different assessment strategies of the TUG was found to have an important impact on outcome measure, highlighting the averaging of several timed trials in each testing session as a recommended alternative to minimize measurement error and increase reliability in longitudinal assessments. Nevertheless, beyond acceptable reliability, poor trial-to-trial stability of the measure appears to exist, since the ranges of expected variability upon retesting were wide and the incidence of spurious statistical effects was not negligible, especially in longitudinal repeated testing. Conclusion: Limitations may exist in the interpretation of the TUG outputs as part of longitudinal assessments aimed at evaluating treatment effectiveness in PD population. Researchers and practitioners should be aware of these concerns to prevent possible misrepresentations of functional ability in patients for a particular intervention. Show more

Keywords: Absolute reliability, intervention, learning effects, long-term, measurement error, minimal detectable change, relative reliability

DOI: 10.3233/JPD-212687

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2047-2055, 2021

Authors: Albrecht, Franziska | Pereira, Joana B. | Mijalkov, Mite | Freidle, Malin | Johansson, Hanna | Ekman, Urban | Westman, Eric | Franzén, Erika

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week …period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects. Show more

Keywords: Randomized controlled trial, magnetic resonance imaging, idiopathic Parkinson’s disease, gait, physical exercise, putamen, gray matter

DOI: 10.3233/JPD-212801

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2057-2071, 2021

Authors: Padmanabhan, Purnima | Sreekanth Rao, Keerthana | Gonzalez, Anthony J. | Pantelyat, Alexander Y. | Chib, Vikram S. | Roemmich, Ryan T.

Article Type: Research Article

Abstract: Background: Gait slowing is a common feature of Parkinson’s disease (PD). Many therapies aim to improve gait speed in persons with PD, but goals are often imprecise. How fast should each patient walk? And how do persons with PD benefit from walking faster? There is an important need to understand how walking speed affects fundamental aspects of gait—including energy cost and stability—that could guide individualized therapy decisions in persons with PD. Objective: We investigated how changes in walking speed affected energy cost and spatiotemporal gait parameters in persons with PD. We compared these effects between dopaminergic medication states …and to those observed in age-matched control participants. Methods: Twelve persons with PD and twelve control participants performed treadmill walking trials spanning at least five different speeds (seven speeds were desired, but not all participants could walk at the fastest speeds). Persons with PD participated in two walking sessions on separate days (once while optimally medicated, once after 12-hour withdrawal from dopaminergic medication). We measured kinematic and metabolic data across all trials. Results: Persons with PD significantly reduced energy cost by walking faster than their preferred speeds. This held true across medication conditions and was not observed in control participants. The patient-specific walking speeds that reduced energy cost did not significantly affect gait variability metrics (used as proxies for gait stability). Conclusion: The gait slowing that occurs with PD results in energetically suboptimal walking. Rehabilitation strategies that target patient-specific increases in walking speed could result in a less effortful gait. Show more

Keywords: Gait, Parkinson’s disease, rehabilitation, energy, dopamine

DOI: 10.3233/JPD-212613

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2073-2084, 2021

Authors: Kumar, Srishti | Shen, Julia W. | Grimes, David | Mestre, Tiago | Thavorn, Kednapa

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a complex and debilitating condition that requires care from a multispecialty team. The Integrated Parkinson Care Network (IPCN) is an innovative pragmatic care model that focuses on integrated care, self-management support and technology-enabled care. Objective: This study aims to estimate the costs of the IPCN and assess whether benefits gained from the intervention offset its costs based on a single center experience. Methods: We conducted a return on investment (ROI) analysis of the IPCN from a societal perspective. The ROI for the IPCN was estimated as a ratio …of the net savings and the intervention cost. The intervention cost was calculated as a sum of set-up and implementation costs. Cost savings was measured as the absolute reduction in the societal costs realized by PD patients. A positive ROI indicated that savings generated from the intervention offset its cost. Results: The total cost of the IPCN for 100 PD patients was C$135,669, or C$226 per patient per month. IPCN was associated with the reduction in societal cost of C$915 per patient per month (95%CI: –2,782, 951). The ROI per PD patient per month for the IPCN was 3.08 (95%CI: –0.60, 22.93), suggesting that for every C$1 invested in the IPCN, C$4.08 is gained through reduction in societal costs. The returns were greater among advanced PD patients. Conclusion: The IPCN has the potential to offer a good return on investment for PD patients, and its value for money is higher among advanced PD patients. Show more

Keywords: Economic evaluation, Parkinson’s disease, integrated care, self-management support, technology-enabled care

DOI: 10.3233/JPD-212578

Citation: Journal of Parkinson's Disease, vol. 11, no. 4, pp. 2085-2091, 2021